T cell-derived Protein S negatively feeds back on dendritic cells to maintain immune homeostasis

EUGENIO ANTONIO CARRERA SILVA; PAMELA CHAN; LEONEL JOANNAS; ARNALDO ARMESTO; ANDREA ERRASTI; CARLA ROTHLIN

New Haven, CT, USA

Jornada; The Annual Retreat of the Human and Translational Immunology; 2012

Yale University

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;} @font-face {font-family:Cambria; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1073743103 0 0 415 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Cambria; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Cambria; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-family:Cambria; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Cambria; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} @page WordSection1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.WordSection1 {page:WordSection1;} --> The innate immune response to pathogens represents the first line of immune defense and triggers the initiation of adaptive immunity. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), play a central role in the activation of dendritic cells (DC) and trigger the subsequent induction of the adaptive immune response. Its fundamental role notwithstanding, DC activation must be tightly regulated to prevent an exacerbated immune response. While reduced DC function leads to increased susceptibility to infections, other pathological conditions, such as allergy, autoimmunity and chronic inflammatory diseases, are often associated with an overactive DC response, underscoring the importance of physiological levels of DC activation for a balanced immune response. Here we show that T cell-derived Protein S (Pros1) tempers DC function and regulates the magnitude of the immune response. Murine and human T cells, when activated, express Pros1. T cell-derived Pros1 dampens DC activation via the TAM receptor tyrosine kinases. The genetic ablation of Pros1 in T cells leads to heightened DC activation and enhanced adaptive immune responses in vivo. Our results identify Pros1 as an anti-inflammatory protein and elucidate a hitherto unknown homeostatic mechanism for the regulation of DC function by the adaptive immune axis.